Kates Steven A, Casale Ralph A, Baguisi Alexander, Beeuwkes Reinier
Ischemix, LLC, 63 Great Road, Maynard, MA 01759, United States.
Ischemix, LLC, 63 Great Road, Maynard, MA 01759, United States.
Bioorg Med Chem. 2014 Jan 1;22(1):505-12. doi: 10.1016/j.bmc.2013.10.057. Epub 2013 Nov 14.
Lipoic acid (1,2-dithiolane-3-pentanoic acid) is a pharmacophore with unique antioxidant and cytoprotective properties. We synthesized a library based upon the condensation of natural and unnatural amino acids with the carboxylic acid moiety of lipoic acid. SAR studies were conducted using a cardiac ischemia-reperfusion animal model. Cytoprotective efficacy was associated with the R-enantiomer of the dithiolane. Potency of library compounds was dictated by the acidic strength of the adduct. α-N-[(R)-1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine, designated CMX-2043, was chosen for further pharmacologic evaluation.
硫辛酸（1,2 - 二硫杂环戊烷 - 3 - 戊酸）是一种具有独特抗氧化和细胞保护特性的药效基团。我们基于天然和非天然氨基酸与硫辛酸的羧酸部分缩合合成了一个文库。使用心脏缺血再灌注动物模型进行了构效关系研究。细胞保护功效与二硫杂环戊烷的R - 对映体相关。文库化合物的效力由加合物的酸性强度决定。α - N - [（R） - 1,2 - 二硫杂环戊烷 - 3 - 戊酰基] - L - 谷氨酰 - L - 丙氨酸，命名为CMX - 2043，被选作进一步的药理学评估。
